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Monitoring mRNA vaccine antigen expression in vivo using PET/CT.

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This study developed a novel method to visualize mRNA vaccine antigen expression in vivo. The engineered reporter gene allowed noninvasive tracking of vaccine distribution and persistence in preclinical models.

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Area of Science:

  • Biotechnology
  • Immunology
  • Molecular Biology

Background:

  • Noninvasive imaging of mRNA vaccine antigen expression is crucial for vaccine development and evaluation.
  • Current methods lack the ability to track the spatiotemporal dynamics of antigen expression in vivo.

Purpose of the Study:

  • To develop and validate an mRNA-encoded reporter gene system for noninvasive imaging of vaccine antigen expression.
  • To assess the feasibility of using E. coli dihydrofolate reductase (eDHFR) as a PET reporter gene fused to a SARS-CoV-2 spike glycoprotein mRNA vaccine.

Main Methods:

  • Genetically fused eDHFR to a modified SARS-CoV-2 spike glycoprotein (S2PΔf) mRNA vaccine.
  • Imaged antigen expression in female mice and male non-human primates using [18F]fluoropropyl-trimethoprim ([18F]FP-TMP) and positron emission tomography (PET).
  • Assessed immunogenicity of the S2P antigen and immune response against eDHFR.

Main Results:

  • Whole-body PET imaging revealed transient expression of the vaccine antigen at the injection site and draining lymph nodes (dLNs).
  • Fusion of eDHFR did not affect S2P immunogenicity.
  • No humoral or cellular immune responses against eDHFR were detected in either species.

Conclusions:

  • eDHFR serves as a viable mRNA-encoded PET reporter gene for monitoring in vivo mRNA vaccine antigen expression dynamics.
  • This technique offers a promising tool for the clinical translation of mRNA vaccines and therapeutics.
  • Noninvasive visualization of antigen expression can aid in the development and evaluation of novel mRNA-based interventions.